Ionic Liquids in Metal, Photo-, Electro-, and (Bio) Catalysis.

Ionic liquids (ILs) have unique physicochemical properties that make them advantageous for catalysis, such as low vapor pressure, non-flammability, high thermal and chemical stabilities, and the ability to enhance the activity and stability of (bio)catalysts. ILs can improve the efficiency, selectivity, and sustainability of bio(transformations) by acting as activators of enzymes, selectively dissolving substrates and products, and reducing toxicity. They can also be recycled and reused multiple times without losing their effectiveness. ILs based on imidazolium cation are preferred for structural organization aspects, with a semiorganized layer surrounding the catalyst. ILs act as a container, providing a confined space that allows modulation of electronic and geometric effects, miscibility of reactants and products, and residence time of species. ILs can stabilize ionic and radical species and control the catalytic activity of dynamic processes. Supported IL phase (SILP) derivatives and polymeric ILs (PILs) are good options for molecular engineering of greener catalytic processes. The major factors governing metal, photo-, electro-, and biocatalysts in ILs are discussed in detail based on the vast literature available over the past two and a half decades. Catalytic reactions, ranging from hydrogenation and cross-coupling to oxidations, promoted by homogeneous and heterogeneous catalysts in both single and multiphase conditions, are extensively reviewed and discussed considering the knowledge accumulated until now.

Temporal Dynamics Underlying Prelimbic Prefrontal Cortical Regulation of Action Selection and Outcome Evaluation during Risk/Reward Decision-Making.

Risk/reward decision-making is a dynamic process that includes periods of deliberation before action selection and evaluation of the action outcomes that bias subsequent choices. Inactivation of the prelimbic (PL) cortex has revealed its integral role in updating decision biases in the face of changes in probabilistic reward contingencies, yet how phasic PL signals during different phases of the decision process influence choice remains unclear. We used temporally specific optogenetic inhibition to selectively disrupt PL activity coinciding with action selection and outcome phases to examine how these signals influence choice. Male rats expressing the inhibitory opsin eArchT within PL excitatory neurons were well trained on a probabilistic discounting task, entailing choice between small/certain versus large/risky rewards, the probability of which varied over a session (50-12.5%). During testing, brief light pulses suppressed PL activity before choice or after different outcomes. Prechoice suppression reduced bias toward more preferred/higher utility options and disrupted how recent outcomes influenced subsequent choice. Inhibition during risky losses induced a similar profile, but here, the impact of reward omissions were either amplified or diminished, relative to the context of the estimated profitability of the risky option. Inhibition during large or small reward receipt reduced risky choice when this option was more profitable, suggesting these signals can both reinforce rewarded risky choices and also act as a relative value comparator signal that augments incentive for larger rewards. These findings reveal multifaceted contributions by the PL in implementing decisions and integrating action-outcome feedback to assign context to the decision space.SIGNIFICANCE STATEMENT The PL prefrontal cortex plays an integral role in guiding risk/reward decisions, but how activity in this region during different phases of the decision process influences choice is unclear. By using temporally specific optogenetic manipulations of this activity, the present study unveiled previously uncharacterized and differential contributions by PL in implementing decision policies and how evaluation of decision outcomes shape subsequent choice. These findings provide novel insight into the dynamic processes engaged by the PL that underlie action selection in situations involving reward uncertainty that may aid in understanding the mechanism underlying normal and aberrant decision-making processes.

Chronic shedding of a SARS-CoV-2 Alpha variant in wastewater.

BACKGROUND: Central Michigan University (CMU) participated in a state-wide SARS-CoV-2 wastewater monitoring program since 2021. Wastewater samples were collected from on-campus sites and nine off-campus wastewater treatment plants servicing small metropolitan and rural communities. SARS-CoV-2 genome copies were quantified using droplet digital PCR and results were reported to the health department. RESULTS: One rural, off-campus site consistently produced higher concentrations of SARS-CoV-2 genome copies. Samples from this site were sequenced and contained predominately a derivative of Alpha variant lineage B.1.1.7, detected from fall 2021 through summer 2023. Mutational analysis of reconstructed genes revealed divergence from the Alpha variant lineage sequence over time, including numerous mutations  in the Spike RBD and NTD. CONCLUSIONS: We discuss the possibility that a chronic SARS-CoV-2 infection accumulated adaptive mutations that promoted long-term infection. This study reveals that small wastewater treatment plants can enhance resolution of rare events and facilitate reconstruction of viral genomes due to the relative lack of contaminating sequences.

Label-Free Composition Analysis of Supramolecular Polymer-Nanoparticle Hydrogels by Reversed-Phase Liquid Chromatography Coupled with a Charged Aerosol Detector.

Supramolecular hydrogels formed through polymer-nanoparticle interactions are promising biocompatible materials for translational medicines. This class of hydrogels exhibits shear-thinning behavior and rapid recovery of mechanical properties, providing desirable attributes for formulating sprayable and injectable therapeutics. Characterization of hydrogel composition and loading of encapsulated drugs is critical to achieving the desired rheological behavior as well as tunable in vitro and in vivo payload release kinetics. However, quantitation of hydrogel composition is challenging due to material complexity, heterogeneity, high molecular weight, and the lack of chromophores. Here, we present a label-free approach to simultaneously determine hydrogel polymeric components and encapsulated payloads by coupling a reversed phase liquid chromatographic method with a charged aerosol detector (RPLC-CAD). The hydrogel studied consists of modified hydroxypropylmethylcellulose, self-assembled PEG-b-PLA nanoparticles, and a therapeutic compound, bimatoprost. The three components were resolved and quantitated using the RPLC-CAD method with a C4 stationary phase. The method demonstrated robust performance, applicability to alternative cargos (i.e., proteins) and was suitable for composition analysis as well as for evaluating in vitro release of cargos from the hydrogel. Moreover, this method can be used to monitor polymer degradation and material stability, which can be further elucidated by coupling the RPLC method with (1) a multi-angle light scattering detector (RPLC-MALS) or (2) high resolution mass spectrometry (RPLC-MS) and a Fourier-transform based deconvolution algorithm. We envision that this analytical strategy could be generalized to characterize critical quality attributes of other classes of supramolecular hydrogels, establish structure-property relationships, and provide rational design guidance in hydrogel drug product development.

Predicting Long-Term Stability of an Oral Delivered Antibody Drug Product with Accelerated Stability Assessment Program Modeling.

The oral delivery of protein therapeutics offers numerous advantages for patients but also presents significant challenges in terms of development. Currently, there is limited knowledge available regarding the stability and shelf life of orally delivered protein therapeutics. In this study, a comprehensive assessment of the stability of an orally delivered solid dosage variable domain of heavy-chain antibody (VHH antibody) drug product was conducted. Four stability related quality attributes that undergo change as a result of thermal and humidity stress were identified. Subsequently, these attributes were modeled using an accelerated stability approach facilitated by ASAPprime software. To the best of our knowledge, this is the first time that this approach has been reported for an antibody drug product. We observed overall good model quality and accurate predictions regarding the protein stability during storage. Notably, we discovered that protein aggregation, formed through a degradation pathway, requires additional adjustments to the modeling method. In summary, the ASAP approach demonstrated promising results in predicting the stability of this complex solid-state protein formulation. This study sheds light on the stability and shelf life of orally delivered protein therapeutics, addressing an important knowledge gap in the field.

Harnessing nanotechnology to expand the toolbox of chemical biology.

Although nanotechnology often addresses biomedical needs, nanoscale tools can also facilitate broad biological discovery. Nanoscale delivery, imaging, biosensing, and bioreactor technologies may address unmet questions at the interface between chemistry and biology. Currently, many chemical biologists do not include nanomaterials in their toolbox, and few investigators develop nanomaterials in the context of chemical tools to answer biological questions. We reason that the two fields are ripe with opportunity for greater synergy. Nanotechnologies can expand the utility of chemical tools in the hands of chemical biologists, for example, through controlled delivery of reactive and/or toxic compounds or signal-binding events of small molecules in living systems. Conversely, chemical biologists can work with nanotechnologists to address challenging biological questions that are inaccessible to both communities. This Perspective aims to introduce the chemical biology community to nanotechnologies that may expand their methodologies while inspiring nanotechnologists to address questions relevant to chemical biology.

Impact of interprofessional geriatric teamwork on students' perceptions of older persons and collaborative practice.

Health professions programs lack sufficient exposure to geriatric education in curricula. The Seniors Assisting in Geriatric Education (SAGE) Program exposes interprofessional (IP) teams of health professions students to older adults. To determine the impact of an interprofessional geriatric educational experience on student perceptions of team collaboration and older adults. IP teams of three or four students (n = 662) representing eight disciplines from two institutions were paired with an older adult to promote person-centered care over three semesters. Students completed two online questionnaires (pre- and post-SAGE Program, ~10 min). 136 students completed both questionnaires. Three IP collaborative practice sub-competencies under the Roles & Responsibilities and Interprofessional Communication Core Competencies increased significantly from pre- to post-SAGE Program (p ≤ 0.002). Comparison of the means for attitudes toward geriatric patients revealed statistically significant improvement in one item, Compassion (p < .002). The SAGE Program had a positive impact on IP collaborative practice and attitudes toward older people in some, but not all, areas.

Expression and purification of a cleavable recombinant fortilin from Escherichia coli for structure activity studies.

Complications related to atherosclerosis account for approximately 1 in 4 deaths in the United States and treatment has focused on lowering serum LDL-cholesterol levels with statins. However, approximately 50% of those diagnosed with atherosclerosis have blood cholesterol levels within normal parameters. Human fortilin is an anti-apoptotic protein and a factor in macrophage-mediated atherosclerosis and is hypothesized to protect inflammatory macrophages from apoptosis, leading to subsequent cardiac pathogenesis. Fortilin is unique because it provides a novel drug target for atherosclerosis that goes beyond lowering cholesterol and utilization of a solution nuclear magnetic resonance (NMR) spectroscopy, structure-based drug discovery approach requires milligram quantities of pure, bioactive, recombinant fortilin. Here, we designed expression constructs with different affinity tags and protease cleavage sites to find optimal conditions to obtain the quantity and purity of protein necessary for structure activity relationship studies. Plasmids encoding fortilin with maltose binding protein (MBP), 6-histidine (6His) and glutathione-S-transferase (GST), N- terminal affinity tags were expressed and purified from Escherichia coli (E. coli). Cleavage sites with tobacco etch virus (TEV) protease and human rhinovirus (HRV) 3C protease were assessed. Despite high levels of expression of soluble protein, the fusion constructs were resistant to proteinases without the inclusion of amino acids between the cleavage site and N-terminus. We surveyed constructs with increasing lengths of glycine/serine (GGS) linkers between the cleavage site and fortilin and found that inclusion of at least one GGS insert led to successful protease cleavage and pure fortilin with conserved binding to calcium as measured by NMR.

Self-Assembly of a Triazolylferrocenyl Dendrimer in Water Yields Nontraditional Intrinsic Green Fluorescent Vesosomes for Nanotheranostic Applications.

The promising field of nanomedicine stimulates a continuous search for multifunctional nanotheranostic systems for imaging and drug delivery. Herein, we demonstrate that application of supramolecular chemistry's concepts in dendritic assemblies can enable the formation of advanced dendrimer-based nanotheranostic devices. A dendrimer bearing 81 triazolylferrocenyl terminal groups adopts a more compact shell-like structure in polar solvents with the ferrocenyl peripheral groups backfolding toward the hydrophobic dendrimer interior, while exposing the more polar triazole moieties as the dendritic shell. Akin to lipids, the compact dendritic structure self-assembles into uniform nanovesicles that in turn self-assemble into larger vesosomes in water. The vesosomes emit green nontraditional intrinsic fluorescence (NTIL), which is an emerging property as there are no classical fluorophores in the dendritic macromolecular structure. This work confirms the hypothesis that the NTIL emission is greatly enhanced by rigidification of the supramolecular assemblies containing heteroatomic subluminophores (HASLs) and by the presence of electron rich functional groups on the periphery of dendrimers. This work is the first one detecting NTIL in ferrocenyl-terminated dendrimers. Moreover, the vesosomes are stable in biological medium, are uptaken by cells, and show cytotoxic activity against cancer cells. Accordingly, the self-organization of these dendrimers into tertiary structures promotes the emergence of new properties enabling the same component, in this case, ferrocenyl group, to function as both antitumoral drug and fluorophore.

Pre-existing influenza-specific nasal IgA or nasal viral infection does not affect live attenuated influenza vaccine immunogenicity in children.

The United Kingdom has a national immunization programme which includes annual influenza vaccination in school-aged children, using live attenuated influenza vaccine (LAIV). LAIV is given annually, and it is unclear whether repeat administration can affect immunogenicity. Because LAIV is delivered intranasally, pre-existing local antibody might be important. In this study, we analysed banked samples from a study performed during the 2017/18 influenza season to investigate the role of pre-existing influenza-specific nasal immunoglobulin (Ig)A in children aged 6-14 years. Nasopharyngeal swabs were collected prior to LAIV immunization to measure pre-existing IgA levels and test for concurrent upper respiratory tract viral infections (URTI). Oral fluid samples were taken at baseline and 21-28 days after LAIV to measure IgG as a surrogate of immunogenicity. Antibody levels at baseline were compared with a pre-existing data set of LAIV shedding from the same individuals, measured by reverse transcription-polymerase chain reaction. There was detectable nasal IgA specific to all four strains in the vaccine at baseline. However, baseline nasal IgA did not correlate with the fold change in IgG response to the vaccine. Baseline nasal IgA also did not have an impact upon whether vaccine virus RNA was detectable after immunization. There was no difference in fold change of antibody between individuals with and without an URTI at the time of immunization. Overall, we observed no effect of pre-existing influenza-specific nasal antibody levels on immunogenicity, supporting annual immunization with LAIV in children.

Dorsomedial striatal contributions to different forms of risk/reward decision making.

Optimal decision making involving reward uncertainty is integral to adaptive goal-directed behavior. In some instances, these decisions are guided by internal representations of reward history, whereas in other situations, external cues inform a decision maker about how likely certain actions are to yield reward. Different regions of the frontal lobe form distributed networks with striatal and amygdalar regions that facilitate different types of risk/reward decision making. The dorsal medial striatum (DMS) is one key output region of the prefrontal cortex, yet there have been few preclinical studies investigating the involvement of the DMS in different forms of risk/reward decision making. The present study addressed this issue, wherein separate groups of male rats were trained on one of two tasks where they chose between a small/certain or a large/risky reward. In a probabilistic discounting task, reward probabilities changed systematically over blocks of trials (100-6.25% or 6.25-100%), requiring rats to use internal representations of reward history to guide choice. Cue-guided decision-making was assessed with a "Blackjack" task, where different auditory cues indicated the odds associated with the large/risky option (50 or 12.5%). Inactivation of the DMS with GABA agonists impaired adjustments in choice biases during probabilistic discounting, resulting in either increases or decreases in risky choice as the probabilities associated with the large/risky reward decreased or increased over a session. In comparison, DMS inactivation increased risky choices on poor-odds trials on the Blackjack task, which was associated with a reduced impact that non-rewarded choices had on subsequent choices. DMS inactivation also impaired performance of an auditory conditional discrimination. These findings highlight a previously uncharacterized role for the DMS in facilitating flexible action selection during multiple forms of risk/reward decision making.

Changes in the Proportion of Inhibitory Interneuron Types from Sensory to Executive Areas of the Primate Neocortex: Implications for the Origins of Working Memory Representations.

Neuronal spiking activity encoding working memory (WM) is robust in primate association cortices but weak or absent in early sensory cortices. This may be linked to changes in the proportion of neuronal types across areas that influence circuits' ability to generate recurrent excitation. We recorded neuronal activity from areas middle temporal (MT), medial superior temporal (MST), and the lateral prefrontal cortex (LPFC) of monkeys performing a WM task and classified neurons as narrow (NS) and broad spiking (BS). The ratio NS/BS decreased from MT > MST > LPFC. We analyzed the Allen Institute database of ex vivo mice/human intracellular recordings to interpret our data. Our analysis suggests that NS neurons correspond to parvalbumin (PV) or somatostatin (SST) interneurons while BS neurons are pyramidal (P) cells or vasoactive intestinal peptide (VIP) interneurons. We labeled neurons in monkey tissue sections of MT/MST and LPFC and found that the proportion of PV in cortical layers 2/3 decreased, while the proportion of CR cells increased from MT/MST to LPFC. Assuming that primate CR/CB/PV cells perform similar computations as mice VIP/SST/PV cells, our results suggest that changes in the proportion of CR and PV neurons in layers 2/3 cells may favor the emergence of activity encoding WM in association areas.

Absorption, metabolism and excretion of pictilisib, a potent pan-class I phosphatidylinositol-3-Kinase (PI3K) inhibitor, in rats, dogs, and humans.

The absorption, metabolism and excretion of pictilisib, a selective small molecule inhibitor of class 1 A phosphoinositide 3-kinase (PI3K), was characterized following a single oral administration of [14C]pictilisib in rats, dogs and humans at the target doses of 30 mg/kg, 5 mg/kg and 60 mg, respectively.Pictilisib was rapidly absorbed with Tmax less than 2 h across species. In systemic circulation, pictilisib represented the predominant total radioactivity greater than 86.6% in all species.Total pictilisib and related radioactivity was recovered from urine and faeces in rats, dogs, and human at 98%, 80% and 95%, respectively, with less than 2% excreted in urine and the rest excreted into faeces.In rat and dog, more than 40% of drug-related radioactivity was excreted into the bile suggesting biliary excretion was the major route of excretion. Unchanged pictilisib was a minor component in rat and dog bile. The major metabolite in bile was O-glucuronide of oxidation on indazole moiety (M20, 21% of the dose) in rats and an oxidative piperazinyl ring-opened metabolite M7 (10.8% of the dose) in dogs.Oxidative glutathione (GSH) conjugates (M18, M19) were novel metabolites detected in rat bile, suggesting the potential generation of reactive intermediates from pictilisib. The structure of M18 was further confirmed by NMR to be a N-hydroxylated and GSH conjugated metabolite on the moiety of the indazole ring.

Patient-centred measurement of recovery from day-case surgery using wrist worn accelerometers: a pilot and feasibility study.

This pilot and feasibility study evaluated wrist-worn accelerometers to measure recovery from day-case surgery in comparison with daily quality of recovery-15 scores. The protocol was designed with extensive patient and public involvement and engagement, and delivered by a research network of anaesthesia trainees. Forty-eight patients recruited through pre-operative assessment clinics wore wrist accelerometers for 7 days before (pre-operative) and immediately after elective surgery (early postoperative), and again at 3 months (late postoperative). Validated activity and quality of recovery questionnaires were administered. Raw accelerometry data were archived and analysed using open source software. The mean (SD) number of valid days of accelerometer wear per participant in the pre-operative, early and late postoperative periods were 5.4 (1.7), 6.6 (1.1) and 6.6 (1.0) days, respectively. On the day after surgery, Euclidian norm minus one (a summary measure of raw accelerations), step count, light physical activity and moderate/vigorous physical activity decreased to 57%, 47%, 59% and 35% of baseline values, respectively. Activity increased progressively on a daily basis but had not returned to baseline values by 7 days. Patient questionnaires suggested subjective recovery by postoperative day 3 to 4; however, accelerometry data showed that activity levels had not returned to baseline at this point. All activity measures had returned to baseline by 3 months. Wrist-worn accelerometery is acceptable to patients and feasible as a surrogate measure for monitoring postoperative recovery from day-case surgery. Our results suggest that patients may overestimate their rate of recovery from day-case surgery, which has important implications for future research.

Design, synthesis and photoinduced processes in molecular interlocked photosynthetic [60]fullerene systems.

In natural photosynthesis, the protein backbone directs and positions primary and secondary electron donor and acceptor moieties in the reaction center to control the yield and kinetics of the sequential electron transfer reactions that transform light energy into chemical potential. Organization of the active cofactors is mainly driven by noncovalent interactions between the protein scaffold and the chromophores. Based on the natural system blueprint, several research efforts have investigated π-π stacking, ionic interactions as well as formation of hydrogen and coordinative bonds as noncovalent organizing principles for the assembly of electron donors and acceptors in artificial reaction centers. Introduction of supramolecular concepts into the organization of electron donor-acceptor in artificial photosynthetic models raises the possibility of applying template-directed synthesis techniques to assemble interlocked systems in which the photo-redox components are mechanically rather than covalently linked. Rotaxanes and catenanes are the leading examples of interlocked molecules, whose recent developments in synthetic chemistry have allowed their efficient preparation. Introduction of mechanical bonds into electron donor-acceptor systems allows the study of the interlocked components' submolecular motions and conformational changes, which are triggered by external stimuli, on the thermodynamic and kinetic parameters of photoinduced processes in artificial reaction centers. This Tutorial discusses our efforts in the synthesis and photophysical investigation of rotaxanes and catenanes decorated with peripheral electron donors and [60]fullerene as the acceptor. The assembly of our rotaxanes and catenanes is based on the classic 1,10-phenanthroline-copper(i) metal template strategy in conjunction with the virtues of the Cu(i)-catalyzed-1,3-dipolar cycloaddition of azides and alkynes (the CuAAC or "click" reaction) as the protocol for the final macrocyclization or stoppering reactions of the entwined precursors. Time-resolved emission and transient absorption experiments revealed that upon excitation, our multichromophoric rotaxanes and catenanes undergo a cascade of sequential energy and electron transfer reactions that ultimately yield charge separated states with lifetimes as long as 61 microseconds, thereby mimicking the functions of the natural systems. The importance of the Cu(i) ion (used to assemble the interlocked molecules) as an electronic relay in the photoinduced processes is also highlighted. The results of this research demonstrate the importance of the distinct molecular conformations adopted by rotaxanes and catenanes in the electron transfer dynamics and illustrate the versatility of interlocked molecules as scaffolds for the organization of donor-acceptor moieties in the design of artificial photosynthetic reaction centers.

Glutathione-S-transferase Fusion Protein Nanosensor.

Fusion protein tags are widely used to capture and track proteins in research and industrial bioreactor processes. Quantifying fusion-tagged proteins normally requires several purification steps coupled with classical protein assays. Here, we developed a broadly applicable nanosensor platform that quantifies glutathione-S-transferase (GST) fusion proteins in real-time. We synthesized a glutathione-DNA-carbon nanotube system to investigate glutathione-GST interactions via semiconducting single-walled carbon nanotube (SWCNT) photoluminescence. We found that SWCNT fluorescence wavelength and intensity modulation occurred specifically in response to GST and GST-fusions. The sensor response was dependent on SWCNT structure, wherein mod(n - m, 3) = 1 nanotube wavelength and intensity responses correlated with nanotube diameter distinctly from mod(n - m, 3) = 2 SWCNT responses. We also found broad functionality of this sensor to diverse GST-tagged proteins. This work comprises the first label-free optical sensor for GST and has implications for the assessment of protein expression in situ, including in imaging and industrial bioreactor settings.

Control over the Redox Cooperative Mechanism of Radical Carbene Transfer Reactions for the Efficient Active-Metal-Template Synthesis of [2]Rotaxanes.

A 5,15-bis(1,1'-biphenyl)porphyrin-based molecular clip covalently connected to a ditopic aliphatic ester loop moiety yields a semi-rigid macrocycle with a well-defined cavity. The resulting macrocycle fits the structural requirements for the preparation of porphyrinates capable of promoting formation of C-C bonds. To demonstrate the usefulness of porphyrin-based macrocycles, an active-metal-template synthesis of rotaxanes through a redox non-innocent carbene transfer reaction is described. Coordination of CoII ions into the porphyrin subunit followed by addition of appropriate monodentate nitrogen-based additives to function as axial ligands enables the radical carbene transfer reactions to styrene derivatives to occur exclusively through the cavity of the macrocycle to afford cyclopropane-linked rotaxanes in excellent 95 % yield. Investigation of the product distribution afforded from the rotaxane assembly reaction reveals how the redox cooperative action between the carbene species and the CoII ions can be manipulated to gain control over the radical-type mechanism to favor the productive rotaxane forming process.

A feasibility study of microwave therapy for precancerous actinic keratosis.

BACKGROUND: Actinic keratosis (AK) is a common premalignant skin lesion that can progress to cutaneous squamous cell carcinoma (cSCC). Microwave therapy is an established cancer treatment and has been used for plantar viral warts. OBJECTIVES: To evaluate the efficacy and feasibility of microwave as a treatment for AK. METHODS: Stage I was a dose-setting study, in which seven participants had the dielectric properties of 12 thick and 22 thin AKs assessed for optimization of the microwave dose used for treatment in Stage II. Stage II was a randomized, internally controlled trial evaluating 179 AKs in 11 patients (93 treated, 86 untreated controls) on the scalp/forehead or dorsal hand. Participants received one treatment initially and a repeat treatment to unresolved AKs at week 4. The response was assessed at six visits over 4 months. The primary outcome was partial or complete resolution of the treated AKs. RESULTS: A significantly higher proportion of treated AK areas responded than untreated (90% vs. 15%; P < 0·001). Thin AKs were more responsive than thick AKs. The site did not affect efficacy. Pain was severe, but brief (80% reported pain lasting 'a few seconds only'). Adverse effects were minimal (erythema, n = 6; flaking, n = 3; itch, n = 3). All participants who would chose microwave therapy over their current treatment cited the shorter discomfort period. CONCLUSIONS: Microwave therapy is a portable, safe and effective treatment for AK. An easy-to-deliver, acceptable therapy for AK is attractive as a prevention strategy. While these results are promising, a larger randomized controlled trial is needed against an effective comparator to confirm clinical efficacy and patient acceptability. What is already known about this topic? Actinic keratoses (AKs) are common precancerous skin lesions. Successful treatment of AK can prevent cutaneous squamous cell carcinoma (cSCC). Most topical therapies for AK require repeated application over weeks and drive local skin inflammation, leading to poor compliance. An easy-to-deliver and effective treatment for AK, suitable for use in primary care, could reduce cSCC. What does this study add? Microwave therapy is a feasible, effective treatment for AK. Ninety per cent of treated AKs showed full or partial resolution at 120 days post-treatment. Microwave therapy was painful, but the pain was short-lived (seconds) and this short discomfort period was cited as the main reason that microwave was preferred to their current treatment.

Rb3InCl6: A Monoclinic Double Perovskite Derivative with Bright Sb3+-Activated Photoluminescence.

Here, we present the synthesis and crystal structure of Rb3InCl6 prepared from air stable reagents via a two-step process that proceeds through the intermediate Rb2InCl5·H2O. Rb3InCl6 crystallizes with the Rb3YCl6 structure type (C2/c), which can be derived from the double perovskite structure by noncooperative tilting of isolated [InCl6]3- octahedra. Despite this lowering of symmetry, the optical properties are similar to the cubic double perovskite Cs2NaInCl6. Partial substitution of In3+ with Sb3+ in Rb3InCl6 results in intense cyan-green photoluminescence originating from localized 5s2 to 5s15p1 electronic transitions of [SbCl6]3- polyatomic anions. In comparison with the cubic double perovskite phosphor Cs2NaInCl6:Sb3+, the octahedral tilting distortion increases the electronic isolation of the In/Sb-centered octahedra thus facilitating electron and hole localization on Sb3+ sites, leading to bright photoluminescence. The distorted crystal structure also leads to a larger Stokes shift (1.29 eV) and a corresponding red shift of the emission peak (λmax = 522 nm) compared to the more symmetric Cs2NaInCl6:Sb3+ (Stokes shift ≈ 0.94 eV, λmax = 445 nm).

Vertical transport and tunnelling in rare-earth nitride heterostructures.

We report an investigation of the ferromagnetic semiconductor rare earth nitrides (RENs) for their potential for cryogenic-temperature electronics and spintronics applications. We have identified ohmic contacts suitable for the device structures that demand electron transport through interface layers, and grown REN/insulator/REN heterostructures that display tunnelling characteristics, an enormous 400% tunneling magnetoresistance and a hysteresis promising their exploitation in non-volatile magnetic random access memory.